Molecular dynamics of an asymmetric form of GabR, a bacterial transcriptional regulator.

GabR is a bacterial transcription regulator with a dimeric structure in which each subunit includes a wHTH (winged Helix-Turn-Helix) domain connected through a peptide linker to a large C-terminal domain folded as the enzyme aspartate aminotransferase (AAT). In Bacillus subtilis, GabR activates the genes involved in the metabolism of γ-amino butyric acid (GABA) upon formation of a PLP-GABA adduct. Recently, the crystallographic structure of an asymmetric form of GabR has been solved. This form (semi-holo) has one active site binding PLP as internal aldimine and the other the PLP-GABA complex. This work reports a molecular dynamics (MD) study aimed at understanding the characteristics of the asymmetric GabR form and compare them to the dynamics properties of previously studied symmetric holo (internal PLP aldimine at both active sites) and holo-GABA (containing PLP-GABA adducts) GabRs. Standard molecular dynamics and data analysis techniques have been used. The results indicate a remarkable asymmetry in the mobility and interactions of the different structural portions of the semi-holo GabR and of a few residues at the active site. The pattern is different from that observed in the other symmetrical GabR forms. The asymmetric perturbation of the active site residues may suggest the existence of a form of allosteric interference between the two active sites.

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